Ms Weix and Dr. Förger contributed equally to this work.
Influence of pregnancy on the adipocytokine and peroxisome proliferator–activated receptor pathways in peripheral blood mononuclear cells from healthy donors and rheumatoid arthritis patients
Article first published online: 26 JUN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 7, pages 2095–2103, July 2012
How to Cite
Weix, J., Förger, F., Häupl, T., Surbek, D., Østensen, M. and Villiger, P. M. (2012), Influence of pregnancy on the adipocytokine and peroxisome proliferator–activated receptor pathways in peripheral blood mononuclear cells from healthy donors and rheumatoid arthritis patients. Arthritis & Rheumatism, 64: 2095–2103. doi: 10.1002/art.34375
- Issue published online: 26 JUN 2012
- Article first published online: 26 JUN 2012
- Accepted manuscript online: 9 JAN 2012 11:58AM EST
- Manuscript Accepted: 3 JAN 2012
- Manuscript Received: 4 AUG 2011
- Swiss National Science Foundation. Grant Number: SNF 320030-116273
- Kurt and Senta Herrmann Foundation
- Olga Mayenfisch Foundation
- University Hospital, Bern (Department of Rheumatology and Clinical Immunology research funding)
To identify candidate genes that are regulated by human pregnancy and have the potential to modulate rheumatoid arthritis (RA) disease activity.
Peripheral blood mononuclear cells (PBMCs) from healthy pregnant volunteers were analyzed using Affymetrix GeneChips at 4 time points (during the first, second, and third trimesters and 6 weeks postpartum). Based on the GeneChip data, target genes were further analyzed via real-time quantitative polymerase chain reaction (qPCR) using PBMCs from healthy controls and RA patients. In order to determine the cellular source of the candidate gene messenger RNA (mRNA), monocytes and lymphocytes from healthy controls and RA patients were positively selected using magnetic beads, and their mRNA was analyzed by qPCR.
One-way analysis of variance identified 1,286 mRNAs that were differentially expressed with regard to the 4 time points. The changes became more pronounced as pregnancy progressed, and they were reversed postpartum. A subsequent pathway analysis suggested a regulatory role of pregnancy on the adipocytokine pathway as well as on the peroxisome proliferator–activated receptor (PPAR) signaling pathway. Of 19 preselected candidate genes, AKT3, SOCS3, FADS2, STAT1, and CD36 proved to be differentially regulated by pregnancy. In samples from RA patients, the differences were concordant with those in healthy controls but more pronounced. Both T lymphocytes and monocytes contributed to the regulated expression of these genes.
Our findings indicate that normal human pregnancy leads to changes in the expression of several molecular pathways in PBMCs, which are reversed postpartum. Changes in RA patients, although concordant, exceed the levels observed in healthy controls. Genes of the adipocytokine and PPAR signaling pathways qualify as candidates for the modulation of RA disease activity during pregnancy.